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1.  Association of Prior Stroke with Cognitive Function and Cognitive Impairment: A Population-based Study 
Archives of neurology  2009;66(5):614-619.
Background
Defining the nature of the contribution of stroke to cognitive impairment remains challenging.
Methods
We randomly selected Olmsted County, MN residents aged 70–89 years on October 1, 2004 and invited eligible non-demented subjects to participate. Participants (n = 2,050) were evaluated with an informant interview, a neurological evaluation, and neuropsychological testing. Neuropsychological testing included 9 tests to assess memory, attention and executive function, visuospatial cognition and language. Subjects were diagnosed by consensus as cognitively normal, MCI (either amnestic (a-) or non-amnestic (na-)), or dementia. A history of stroke was obtained from the subject and confirmed in the medical record. We computed the odds ratios (OR) for a clinical diagnosis of MCI or for scoring in the lowest quartile on each cognitive domain.
Results
There were 1640 cognitively normal and 329 MCI subjects, 241 a-MCI and 88 na-MCI. In fully adjusted models with non-demented subjects only, a history of stroke was associated with a higher odds ratio (OR) of na-MCI (OR= 2.85, 95% CI 1.61 – 5.04) than a-MCI (OR= 1.77, 95% CI 1.14 – 2.74). A history of stroke was also associated with impaired function in each cognitive domain except memory. The association was strongest for attention and executive function (OR=2.48, 95% CI 1.73 – 3.53). APOE e4 genotype was associated only with a-MCI and with impaired memory function.
Conclusions
In this population-based sample of non-demented persons, a history of stroke was particularly associated with na-MCI and with impairment in non-memory cognition. APOE e4 genotype was associated with memory impairment and a-MCI.
doi:10.1001/archneurol.2009.30
PMCID: PMC3050015  PMID: 19433661
2.  Physical Exercise and Mild Cognitive Impairment: A Population-Based Study 
Archives of neurology  2010;67(1):80-86.
Objective
Physical exercise was found to be associated with a decreased risk of dementia and Alzheimer disease. We investigated whether physical exercise is also associated with mild cognitive impairment (MCI).
Design
Population-based case-control study.
Setting
The Mayo Clinic Study of Aging, an ongoing population-based cohort study in Olmsted County, Minnesota, USA.
Participants
1324 non-demented subjects who completed a questionnaire on physical exercise.
Main Outcome Measures
An expert consensus panel classified each subject as either cognitively normal or affected by MCI using information from a Clinical Dementia Rating Scale administered to the subject and to an informant, a neurological evaluation, and neuropsychological testing to assess 4 cognitive domains.
Results
We compared the frequency of physical exercise in 198 subjects with MCI to the frequency in 1126 cognitively normal subjects and adjusted analyses for age, sex, years of education, medical comorbidity, and depression. The odds ratio (OR) for any frequency of moderate-intensity exercise was 0.61 (95% confidence interval [CI], 0.43–0.88; P=.008) for exercise in midlife (aged 50–65 years), and 0.68 (95% CI, 0.49–0.93; P=.02) for exercise in late life. The findings were consistent in men and women. Light exercise and vigorous exercise were not significantly associated with MCI.
Conclusions
In this population-based case-control study, any frequency of moderate-intensity exercise carried out in either midlife or late life was associated with a reduced OR of MCI.
doi:10.1001/archneurol.2009.297
PMCID: PMC2919839  PMID: 20065133
3.  Metabolic Syndrome, Inflammation, and Non-Amnestic Mild Cognitive Impairment in Older Persons: A Population-Based Study 
The metabolic syndrome (MetS) is more strongly associated with cognitive impairment in the presence of inflammation. This suggests that the association of MetS with mild cognitive impairment (MCI) may vary with the etiology and the subtype of MCI. This study investigated the association between MetS with or without inflammation and MCI (amnestic [a-MCI] and non-amnestic [na-MCI]). We studied a randomly selected sample of 1969 subjects (ages 70 to 89 years) from Olmsted County, MN, using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Data for participants were reviewed for a diagnosis of normal cognition, MCI, or dementia. Clinical components of MetS were ascertained by interview and confirmed from the medical records; biochemical measurements were assayed from a blood draw. We compared 88 na-MCI cases and 241 a-MCI cases with 1640 cognitively normal subjects. MetS was not associated with either na-MCI or a-MCI. High C-reactive protein (CRP highest tertile vs lowest tertile) was associated with na-MCI (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 1.05, 3.24) but not with a-MCI, after adjusting for sex, age, and years of education. The combination of MetS and high CRP (compared to no Mets and lowest CRP tertile) was associated with na-MCI (OR = 2.31; 95% CI = 1.07, 5.00), but not with a-MCI (OR = 0.96; 95% CI = 0.59, 1.54). The combined presence of MetS and high levels of inflammation is associated with na-MCI in this elderly cohort, and suggests etiologic differences in MCI subtypes.
doi:10.1097/WAD.0b013e3181a4485c
PMCID: PMC2837096  PMID: 19568151
metabolic syndrome; insulin resistance; mild cognitive impairment; C-reactive protein; inflammation; cross-sectional study
4.  The Prevalence of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Normal Cognitive Aging: A Population-Based Study 
Archives of general psychiatry  2008;65(10):1193-1198.
Context
Little is known about the population-based prevalence of neuropsychiatric symptoms in mild cognitive impairment (MCI).
Objective
To estimate the prevalence of neuropsychiatric symptoms in MCI and normal cognitive aging in a defined population.
Design
Cross-sectional study derived from an ongoing population-based prospective cohort study.
Setting
The Mayo Clinic Study of Aging.
Participants
We studied a random sample of 1969 non-demented participants out of the target population of 9965 elderly persons residing in Olmsted County on the prevalence date (October 1, 2004). Neuropsychiatric data were available on 319 of the 329 MCI subjects (97.0%) and on 1590 of the 1640 cognitively normal subjects (97.0%).
Method
Neurological, cognitive, and neuropsychiatric data were gathered from the study participants. A classification of normal cognitive aging, MCI, and dementia was adjudicated by an expert consensus panel. Accordingly, 329 subjects were classified as having MCI and the remaining 1640 subjects were classified as cognitively normal.
Main Outcome Measure
The Neuropsychiatric Inventory Questionnaire (NPI-Q).
Results
Multi-variable logistic regression analyses were conducted, after adjusting for age, sex, and education. By taking into consideration both the odds ratio and the frequency of a symptom, the most distinguishing features between the 2 groups were apathy (odds ratio [OR], 4.53; 95% confidence interval [95% CI], 3.11–6.60; P<.001), agitation (OR, 3.60; 95% CI, 2.18–5.92; P<.001), anxiety (OR, 3.00; 95% CI, 2.01–4.48; P<.001), irritability (OR, 2.99; 95% CI, 2.11–4.22; P<.001), and depression (OR, 2.78; 95% CI, 2.06–3.76; P<.001). Delusion had the highest OR (8.12; 95% CI, 2.92–22.60; P<.001); however, it was rare in both cognitively normal subjects (6/1590=0.4%) and MCI (11/319=3.4%). Thus, the population attributable risk for delusion was only 2.62% as compared to 14.60% for apathy.
Conclusions
Non-psychotic symptoms affected approximately 50% of subjects with MCI and 25% of cognitively normal subjects. By contrast, psychotic symptoms were rare.
doi:10.1001/archpsyc.65.10.1193
PMCID: PMC2575648  PMID: 18838636
5.  Computer Activities, Physical Exercise, Aging, and Mild Cognitive Impairment: A Population-Based Study 
Mayo Clinic Proceedings  2012;87(5):437-442.
Objective
To examine the association between computer use, physical exercise, aging, and mild cognitive impairment (MCI).
Patients and Methods
The Mayo Clinic Study of Aging is a population-based study of aging and MCI in Olmsted County, Minnesota. The study sample consists of a random sample of 926 nondemented individuals aged 70 to 93 years who completed self-reported questionnaires on physical exercise, computer use, and caloric intake within 1 year of the date of interview. The study was conducted from April 1, 2006, through November 30, 2008. An expert consensus panel classified each study participant as cognitively normal or having MCI on the basis of published criteria.
Results
Using a multivariable logistic regression model, we examined the impact of the presence during the study period of 2 lifestyle factors (physical exercise and computer use) after adjusting for a third lifestyle factor (caloric intake) on aging and MCI. We also adjusted for age, sex, education, medical comorbidity, and depression. The median daily caloric intake was significantly higher in participants with MCI than in controls (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P=.001). Participants who engaged in both moderate physical exercise and computer use had significantly decreased odds of having MCI (odds ratio [95% confidence interval], 0.36 [0.20-0.68]) compared with the reference group. In the interaction analyses, there was an additive interaction (P=.012) but not multiplicative interaction (P=.780).
Conclusion
In this population-based sample, the presence of both physical exercise and computer use as assessed via survey was associated with decreased odds of having MCI, after adjustment for caloric intake and traditional confounders.
doi:10.1016/j.mayocp.2011.12.020
PMCID: PMC3538471  PMID: 22560523
CDR, Clinical Dementia Rating; CI, confidence interval; MCI, mild cognitive impairment; OR, odds ratio
6.  Subtle Deficits in Instrumental Activities of Daily Living in Subtypes of Mild Cognitive Impairment 
Background/Aims
Greater cognitive and functional deficits in mild cognitive impairment (MCI) are associated with higher rates of dementia. We explored the relationship between these factors by comparing instrumental activities of daily living (IADLs) among cognitive subtypes of MCI and examining associations between IADL and neuropsychological indices.
Methods
We analyzed data from 1,108 MCI and 3,036 normal control subjects included in the National Alzheimer's Coordinating Center Uniform Data Set who were assessed with the Functional Activities Questionnaire (FAQ).
Results
IADL deficits were greater in amnestic than nonamnestic MCI, but within these subgroups, did not differ between those with single or multiple domains of cognitive impairment. FAQ indices correlated significantly with memory and processing speed/executive function.
Conclusions
IADL deficits are present in both amnestic MCI and nonamnestic MCI but are not related to the number of impaired cognitive domains. These cross-sectional findings support previous longitudinal reports suggesting that cognitive and functional impairments in MCI may be independently associated with dementia risk.
doi:10.1159/000313540
PMCID: PMC2948658  PMID: 20798539
Mild cognitive impairment; Functional impairment; Activities of daily living; Memory performance; Executive function
7.  Duration and Severity of Diabetes Are Associated with Mild Cognitive Impairment 
Archives of neurology  2008;65(8):1066-1073.
Background
It remains unknown whether diabetes mellitus is a risk factor for mild cognitive impairment (MCI).
Objective
To investigate the association of diabetes mellitus with MCI using a population-based case-control design.
Design, Setting, and Participants
Our study was conducted in subjects aged 70 through 89 years on October 1, 2004, who were randomly selected from the Olmsted County, MN, population.
Main Outcome Measure
We administered to all participants the Clinical Dementia Rating Scale, a neurological exam, and a neuropsychological evaluation including 9 tests in 4 cognitive domains to diagnose normal cognition, MCI, or dementia. We assessed history of diabetes, diabetes treatment, and complications by interview and we measured fasting blood glucose. History of diabetes was also confirmed using a medical records-linkage system.
Results
We compared 329 patients with MCI to 1640 subjects free of MCI and of dementia. The frequency of diabetes was similar in subjects with MCI (20.1%) and in subjects without MCI (17.7%; odds ratio [OR], 1.16; 95% confidence interval [CI], 0.85-1.57). However, MCI was associated with onset of diabetes before age 65 years (OR, 2.20; 95% CI, 1.29-3.73), diabetes duration ≥10 years (OR, 1.76; 95% CI, 1.16-2.68), treatment with insulin (OR, 2.01; 95% CI, 1.22-3.31), and presence of complications (OR, 1.80; 95% CI, 1.13-2.89) after adjustment for age, sex, and education. Analyses using alternative definitions of diabetes yielded consistent findings.
Conclusions
These findings suggest an association between earlier onset, longer duration, and greater severity of diabetes and MCI.
doi:10.1001/archneur.65.8.1066
PMCID: PMC2630223  PMID: 18695056
8.  Mild Cognitive Impairment in Parkinson’s Disease 
Minerva Medica  2011;102(6):441-459.
While Parkinson’s disease (PD) traditionally has been defined by its characteristic motor hallmarks, non-motor features such as cognitive impairment and dementia are increasingly recognized as part of PD. Mild cognitive impairment is common in non-demented PD patients, occurring in about 20-50%. Frequency estimates and clinical features of mild cognitive impairment in PD (PD-MCI), however, vary across studies due to methodological differences and lack of uniform diagnostic criteria for PD-MCI. Overall, PD-MCI patients exhibit nonamnestic deficits in cognitive domains such as executive function, attention, and visuospatial function; however, the cognitive phenotype of PD-MCI is heterogeneous with some patients demonstrating greater amnestic deficits. PD-MCI patients, particularly those with posterior cortical profiles, may be at high risk for developing dementia. Various biomarkers studied in PD-MCI including cerebrospinal fluid, genetic analyses, and neuroimaging suggest that there may be distinct PD-MCI profiles. Future studies using uniform PD-MCI diagnostic criteria and incorporating biomarkers and longitudinal follow-up of PD-MCI cohorts are needed to understand PD-MCI as a transitional state between normal cognition and dementia.
PMCID: PMC3370887  PMID: 22193376
Parkinson’s disease; dementia; mild cognitive impairment; executive dysfunction; cognitive domains
9.  Neuropsychiatric symptoms in MCI subtypes: the importance of executive dysfunction 
Objective
Mild cognitive impairment (MCI) is a syndrome thought to be a prodrome of dementia for some patients. One subtype, amnestic MCI, may be specifically predispose patients to develop Alzheimer’s Dementia (AD). Since dementia has been associated with a range of neuropsychiatric symptoms (NPS), we sought to examine the prevalence of NPS in MCI and its subtypes.
Methods
1779 participants in the National Alzheimer Coordinating Center (NACC) with MCI were included in this study. All participants were evaluated systematically with a thorough cognitive battery, clinical interview, and consensus diagnoses, and subtyped as: 1) amnestic (aMCI) (single- or multiple-domain) vs. non-amnestic (non-aMCI); 2) executive dysfunction-MCI (exMCI) (single- or multiple-domain) vs. no executive dysfunction-MCI (non-exMCI); 3) both aMCI and exMCI; 4) and neither aMCI nor exMCI. Additionally , aMCI vs. nonaMCI and exMCI vs. non-exMCI dichotomies were explored. NPS were assessed with the Neuropsychiatric Inventory (NPI-Q) and Geriatric Depression Scale (GDS).
Results
1379 participants (77.5%) met criteria for aMCI and 616 (34.6%) for exMCI. No differences were observed in the prevalence of NPS between aMCI vs. non-aMCI. However, exMCI was associated with greater severity of depression, anxiety, agitation, disinhibition, irritability, and sleep problems, although these differences do not persist after adjustment for several variables. .
Conclusions
While there were few associations between aMCI and NPS, the presence of executive dysfunction in MCI was associated with greater severity of symptoms and specifically with depression (evidenced by GDS score) and anxiety. These findings may have implications for MCI prognosis and need to be explored in longitudinal studies.
doi:10.1002/gps.2535
PMCID: PMC3204866  PMID: 20845402
Mild Cognitive Impairment; Depression; Executive Dysfunction; Neuropsychiatric symptoms
10.  FUNCTIONAL AND COGNITIVE CRITERIA PRODUCE DIFFERENT RATES OF MCI AND CONVERSION TO DEMENTIA 
Objective
To compare rates of Mild Cognitive Impairment (MCI) and rates of progression to dementia, using different MCI diagnostic systems
Methods
MCI was investigated at baseline in 3063 community-dwelling non-demented elderly in the Ginkgo Evaluation of Memory (GEM) study who were evaluated every six months to identify presence of dementia. Overall MCI frequency was determined using (1) Clinical Dementia Rating (CDR) score of 0.5 and (2) neuropsychological (NP) criteria, defined by impairment on standard cognitive tests.
Results
40.2% of participants met CDR MCI criteria and 28.2% met NP MCI criteria (amnestic-MCI=16.6%). 15.7% were classified as MCI by both criteria and 47.4% as Normal by both. Discordant diagnoses were observed in 24.5% who met NP Normal/CDR MCI; and 12.4% who met NP MCI/CDR Normal. Factors associated with CDR MCI among NP Normal included, lower education, lower NP scores, more IADL impairment, greater symptoms of depression and subjective health problems. Individuals meeting NP MCI/CDR normal were significantly more likely to develop dementia over the median follow up of 6.1 years than those meeting NP Normal/CDR MCI.
Conclusions
Different criteria produce different MCI rates and different conversion rates to dementia. Although a higher percentage of MCI was identified by CDR than NP, a higher percentage of NP MCI progressed to dementia. These findings suggest that the CDR is sensitive to subtle changes in cognition not identified by NP algorithm but is also sensitive to demographic and clinical factors probably leading to a greater number of false positives. These results suggest that identifying all individuals with CDR scores of 0.5 as Alzheimer's disease is not advisable.
doi:10.1136/jnnp.2008.160705
PMCID: PMC2698042  PMID: 19279031
Clinical Dementia Rating Scale; Neuropsychological tests
11.  Cognitive impairment in non-1 demented oldest-old: Prevalence and relationship to cardiovascular risk factors 
Alzheimer's & Dementia  2011;8(2):87-94.
Objective
To determine the prevalence and types of cognitive impairment in a sample of non-demented aged 90 and older (the oldest-old) and to examine the relationships between cognitive impairment and cardiovascular risk factors.
Participants
420 non-demented participants from The 90+ Study, a study of aging and dementia in the oldest-old. Participants were categorized into four non-overlapping groups: normal cognition, amnestic mild cognitive impairment (aMCI), non-amnestic MCI (naMCI), and other cognitive impairment (OCI). History of cardiovascular risk factors was assessed through self-report.
Results
The overall prevalence of cognitive impairment in non-demented was 34.0% (95%CI: 29.5–38.5). The prevalence of OCI was highest (17.4%; 95%CI: 13.9–21.4) followed by aMCI (8.3%; 95%CI: 5.9–11.4) and naMCI (8.3%; 95%CI: 5.9–11.4). Normal cognition was present in 66.0% (95%CI: 61.2–70.5) of participants. History of hypertension and stroke were the only risk factors that varied between the groups, occurring more frequently in participants with naMCI (χ2=3.82; p<0.05) and OCI (χ2=5.51; p<0.05).
Conclusions
This study found a high prevalence of cognitive impairment in a sample of non-demented oldest-old. We did not find a strong relationship between cardiovascular risk factors and the cognitive impairment groups other than between hypertension and naMCI and stroke and OCI. Future studies comparing the incidence of dementia in these groups will ultimately determine their predictive utility in the oldest-old.
doi:10.1016/j.jalz.2011.02.008
PMCID: PMC3276712  PMID: 22055654
mild cognitive impairment; oldest-old; cardiovascular risk factors
12.  Coronary heart disease is associated with non-amnestic mild cognitive impairment 
Neurobiology of aging  2008;31(11):1894-1902.
The progression of amnestic mild cognitive impairment (a-MCI) to Alzheimer’s disease and hypothesized progression of non-amnestic mild cognitive impairment (na-MCI) to non-degenerative or vascular dementias suggest etiologic differences. We examined the association between coronary heart disease (CHD) and mild cognitive impairment (MCI) subtypes in a population-based cohort. Participants (n = 1969; aged 70-89 years) were evaluated using the Clinical Dementia Rating Scale, a neurological examination, and neuropsychological testing for diagnoses of normal cognition, MCI, or dementia. CHD was defined as a history of myocardial infarction, angina, angiographic coronary stenosis, or coronary revascularization and ascertained by participant interview and from medical records. CHD was significantly associated with Na-MCI (OR = 1.93; 95% CI = 1.22-3.06) but not with a-MCI (OR = 0.94; 95% CI = 0.69-1.28). In contrast, ApoE ε4 allele was significantly associated with a-MCI (OR = 1.75; 95% CI = 1.28-2.41), but not with na-MCI (OR = 1.17, 95% CI = 0.69-2.00). The association of CHD with prevalent na-MCI but not with a-MCI suggests that CHD and na-MCI may have similar underlying etiologies.
doi:10.1016/j.neurobiolaging.2008.10.018
PMCID: PMC2888961  PMID: 19091445
Cognitive impairment; Coronary heart disease; Myocardial infarction; Angina; Coronary artery bypass grafting; Population-based
13.  Taking Care of Older Adults with Mild Cognitive Impairment: An Update for Nurses Journal of Gerontological Nursing (in press) 
Mild cognitive impairment (MCI) is a mild decline in single or multiple cognitive domains, while global cognition and basic activities of daily living remain intact. Nurses play an important role in early detection of MCI and providing care to maintain maximum independence for persons with MCI. This update seeks to provide nurses with a review of the most recent research regarding the etiology and diagnosis of MCI, risk and protective factors related to MCI, patients and their families' experience of MCI, and current interventions for persons with MCI. This update provides research evidence to inform nursing practice of MCI care.
doi:10.3928/00989134-20121106-02
PMCID: PMC3587112  PMID: 23189995
Mild Cognitive Impairment; Alzheimer's disease; Instrumental Activities of Daily Living; Cognition; Risk factors; Non-pharmacological interventions
14.  The incidence of MCI differs by subtype and is higher in men 
Neurology  2012;78(5):342-351.
Objective:
Although incidence rates for mild cognitive impairment (MCI) have been reported, few studies were specifically designed to measure the incidence of MCI and its subtypes using published criteria. We estimated the incidence of amnestic MCI (aMCI) and nonamnestic MCI (naMCI) in men and women separately.
Methods:
A population-based prospective cohort of Olmsted County, MN, residents ages 70–89 years on October 1, 2004, underwent baseline and 15-month interval evaluations that included the Clinical Dementia Rating scale, a neurologic evaluation, and neuropsychological testing. A panel of examiners blinded to previous diagnoses reviewed data at each serial evaluation to assess cognitive status according to published criteria.
Results:
Among 1,450 subjects who were cognitively normal at baseline, 296 developed MCI. The age- and sex-standardized incidence rate of MCI was 63.6 (per 1,000 person-years) overall, and was higher in men (72.4) than women (57.3) and for aMCI (37.7) than naMCI (14.7). The incidence rate of aMCI was higher for men (43.9) than women (33.3), and for subjects with ≤12 years of education (42.6) than higher education (32.5). The risk of naMCI was also higher for men (20.0) than women (10.9) and for subjects with ≤12 years of education (20.3) than higher education (10.2).
Conclusions:
The incidence rates for MCI are substantial. Differences in incidence rates by clinical subtype and by sex suggest that risk factors for MCI should be investigated separately for aMCI and naMCI, and in men and women.
doi:10.1212/WNL.0b013e3182452862
PMCID: PMC3280046  PMID: 22282647
15.  Content Validity and Acceptability of the Daily Enhancement of Meaningful Activity Program Intervention for Mild Cognitive Impairment Patient-Spouse Dyads 
Persons with mild cognitive Impairment (PwMCI) are at greater risk for developing Alzheimer’s disease and they experience various difficulties that decrease their quality of life. Very few interventions focus on helping PwMCI improve or maintain functional performance and enhance quality of life through meaningful activity engagement. The purpose of the study was to explore PwMCI and their spouses’ perspectives on the content validity, usefulness, and acceptability of the daily enhancement of meaningful activity (DEMA) program, which included 6 bi-weekly face-to-face sessions, between session assignments, and a self-management tool kit of written educational handouts. Nine PwMCI-care partner dyads participated in three focus groups (PwMCI alone, spouses alone, couples) to capture their perspectives on DEMA. The transcribed focus group data were analyzed through content analysis. The three groups provided support for content validity and acceptability of the program, and they suggested additional content areas important to couples experiencing MCI. They also attested to the usefulness of the tool kit and gave suggestions for its further improvement. The findings provide evidence of the content validity and acceptability of the DEMA program. A pilot study to assess feasibility and preliminary efficacy of the DEMA on health-related outcomes is the recommended next research step for this program.
doi:10.1097/JNN.0b013e318234e9dd
PMCID: PMC3220889  PMID: 22089409
patient care partner; mild cognitive impairment; acceptability of program; program evaluation
16.  Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease in an Asian Memory Clinic – Evidence for a Clinical Spectrum 
Objectives
To determine if mild cognitive impairment (MCI) represents a continuum of cognitive and functional deficits.
Methods
Clinical data of 164 subjects with no dementia (ND, n = 52), uncertain dementia (n = 69), and mild probable Alzheimer's disease (AD, n = 43) were reviewed. Uncertain dementia patients were classified as pre-MCI (n = 11), early amnestic MCI (e-aMCI, n = 15) and late amnestic MCI (l-aMCI, n = 15). Cognitive assessments [Chinese Mini-Mental State Examination (CMMSE) and a validated neuropsychological battery], functional assessments (Lawton's scale for instrumental activities of daily living) and neuroimaging (ischemic lesions and medial temporal lobe atrophy) were reviewed.
Results
ND, aMCI and mild AD subjects demonstrated a significant trend for worsening performance for all cognitive and functional measures (ANOVA, p < 0.05). Pre-MCI subjects performed significantly better than aMCI subjects in all verbal memory domains (p < 0.001), while l-aMCI had worse functional performance (p = 0.007), a trend towards greater depressive symptoms (p = 0.05) and higher medial temporal lobe atrophy scores (p = 0.06). l-aMCI subjects were more likely than either pre-MCI or e-aMCI to progress to dementia over a mean follow-up period of 2.5 years (46.7 vs. 9.1 and 20.0%, respectively).
Conclusions
Clinical delineation of aMCI allows the differentiation of those likely to progress for better correlation to biomarker development.
doi:10.1159/000327519
PMCID: PMC3199896  PMID: 22163238
Alzheimer's disease; Clinical dementia rating; Disease spectrum; Mild cognitive impairment
17.  Complex activities of daily living vary by mild cognitive impairment subtype 
There is increasing consensus regarding the importance of operationally defining and measuring functional decline in mild cognitive impairment (MCI). However, few studies have directly examined functional abilities in MCI or its presumed subtypes and, to date, reported findings have been discrepant. Nondemented older adults (n = 120) were administered a comprehensive cognitive battery measuring multiple domains as well as a performance-based functional ability measure. Participants were characterized as either cognitively normal, amnestic MCI, or non-amnestic MCI. MCI individuals demonstrated decrements in instrumental activities of daily living (IADL) relative to their cognitively normal counterparts. Specifically, participants with amnestic MCI demonstrated significant decrements in financial management, whereas those with non-amnestic MCI showed poorer performance in abilities related to health and safety. Moreover, decreased functional abilities were associated with decrements in global cognitive functioning but not memory or executive functions in the MCI participants. Finally, logistic regression demonstrated that functional abilities accurately predicted MCI subtype. Results support the need for better delineation of functional decline in MCI. Given the implications of functional status for MCI diagnosis and treatment, the direct assessment of functional abilities is recommended. Results further suggest performance-based IADL assessment may have utility in distinguishing MCI subtypes.
doi:10.1017/S1355617710000330
PMCID: PMC2891154  PMID: 20374675
Mild cognitive impairment; Older adults; Neuropsychology; Activities of daily living; Amnestic; Nonamnestic
18.  Prevalence of mild cognitive impairment is higher in men 
Neurology  2010;75(10):889-897.
Objective:
We investigated the prevalence of mild cognitive impairment (MCI) in Olmsted County, MN, using in-person evaluations and published criteria.
Methods:
We evaluated an age- and sex-stratified random sample of Olmsted County residents who were 70–89 years old on October 1, 2004, using the Clinical Dementia Rating Scale, a neurologic evaluation, and neuropsychological testing to assess 4 cognitive domains: memory, executive function, language, and visuospatial skills. Information for each participant was reviewed by an adjudication panel and a diagnosis of normal cognition, MCI, or dementia was made using published criteria.
Results:
Among 1,969 subjects without dementia, 329 subjects had MCI, with a prevalence of 16.0% (95% confidence interval [CI] 14.4–17.5) for any MCI, 11.1% (95% CI 9.8–12.3) for amnestic MCI, and 4.9% (95% CI 4.0–5.8) for nonamnestic MCI. The prevalence of MCI increased with age and was higher in men. The prevalence odds ratio (OR) in men was 1.54 (95% CI 1.21–1.96; adjusted for age, education, and nonparticipation). The prevalence was also higher in subjects who never married and in subjects with an APOE ε3ε4 or ε4ε4 genotype. MCI prevalence decreased with increasing number of years of education (p for linear trend <0.0001).
Conclusions:
Our study suggests that approximately 16% of elderly subjects free of dementia are affected by MCI, and amnestic MCI is the most common type. The higher prevalence of MCI in men may suggest that women transition from normal cognition directly to dementia at a later age but more abruptly.
GLOSSARY
= Alzheimer disease;
= amnestic mild cognitive impairment;
= Clinical Dementia Rating scale;
= confidence interval;
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= Functional Activities Questionnaire;
= mild cognitive impairment;
= nonamnestic mild cognitive impairment;
= odds ratio;
= Short Test of Mental Status;
= Telephone Interview for Cognitive Status-modified;
= Wechsler Adult Intelligence Scale-Revised.
doi:10.1212/WNL.0b013e3181f11d85
PMCID: PMC2938972  PMID: 20820000
19.  Association of C-reactive protein with mild cognitive impairment 
Background
Inflammation is suggested to play a role in the development of Alzheimer’s disease, and may also be involved in the pathogenesis of mild cognitive impairment (MCI). This study examined the association of inflammatory markers in serum or plasma with prevalent MCI and MCI subtypes in a population-based sample.
Methods
Olmsted County, MN, residents aged 70–89 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Information ascertained for each participant was reviewed by an expert panel of neuropsychologists, physicians, and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by consensus. C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis alpha (TNFα), and adiponectin were measured at baseline.
Results
Among 313 subjects with MCI and 1,570 cognitively normal subjects, a CRP level in the upper quartile (> 3.3 mg/L) was significantly associated with MCI (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.00–2.01) and with non-amnestic MCI (na-MCI; OR, 2.05; 95% CI, 1.12–3.78) after adjusting for age, sex, and years of education. However, there was no association with amnestic MCI (a-MCI; OR, 1.21; 95% CI, 0.81–1.82). No association was observed with the other inflammatory markers.
Conclusions
Plasma CRP is associated with prevalent MCI and with na-MCI in elderly, non-demented persons in the population-based setting. These findings suggest an involvement of inflammation in the pathogenesis of MCI.
doi:10.1016/j.jalz.2009.01.025
PMCID: PMC2851170  PMID: 19751919
C-reactive protein; Interleukin 6; Adiponectin; Inflammation; Cytokines; Mild cognitive impairment; Cross-sectional; Population-based
20.  Electromyographic Activity in the EEG in Alzheimer's Disease: Noise or Signal? 
Many efforts have been directed at negating the influence of electromyographic (EMG) activity on the EEG, especially in elderly demented patients. We wondered whether these “artifacts” might reflect cognitive and behavioural aspects of dementia. In this pilot study, 11 patients with probable Alzheimer's disease (AD), 13 with amnestic mild cognitive impairment (MCI) and 13 controls underwent EEG registration. As EMG measures, we used frontal and temporal 50–70 Hz activity. We found that the EEGs of AD patients displayed more theta activity, less alpha reactivity, and more frontal EMG than controls. Interestingly, increased EMG activity indicated more cognitive impairment and more depressive complaints. EEG variables on the whole distinguished better between groups than EMG variables, but an EMG variable was best for the distinction between MCI and controls. Our results suggest that EMG activity in the EEG could be more than noise; it differs systematically between groups and may reflect different cerebral functions than the EEG.
doi:10.4061/2011/547024
PMCID: PMC3089836  PMID: 21559240
21.  Changes in everyday function among individuals with psychometrically defined Mild Cognitive Impairment in the ACTIVE Study 
Objectives.
Because many individuals with Mild Cognitive Impairment (MCI) will progress to a dementia diagnosis, this population is at high risk for losing functional independence. We examine trajectories of change in everyday function for individuals with cognitive deficits suggestive of MCI.
Design.
We utilized data from the longitudinal, multi-site Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, which allowed for post-hoc classification of MCI status at baseline using psycho metric definitions for amnestic MCI, non-amnestic MCI, multi-domain MCI, and no MCI.
Setting.
Six U.S. cities.
Participants.
2832 volunteers (mean age 74 years; 26% African American) living independently, recruited from senior housing, community centers, and hospitals and clinics.
Measurements.
Mixed effect models examined changes in self-reported instrumental and basic activities of daily living (IADLs and ADLs) from the MDS Home Care Interview in 2,358 participants over a three-year period.
Results.
In models for IADL performance, IADL difficulty, and a Daily Functioning Composite, there was a significant time by MCI classification interaction for each MCI subtype, indicating that all MCI groups showed faster rates of decline in everyday function relative to cognitively normal participants with no MCI.
Conclusion.
Results demonstrate the importance of MCI as a clinical entity that not only predicts progression to dementia but also predicts functional declines in activities that are key to autonomy and quality of life. MCI classification guidelines should allow for functional changes in MCI, and clinicians should monitor for such changes. Preservation of function may serve as a meaningful outcome for intervention efforts.
doi:10.1111/j.1532-5415.2007.01245.x
PMCID: PMC2153444  PMID: 17661957
Mild Cognitive Impairment; functional change; ADL; IADL
22.  Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal 
Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer’s disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants’ activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly-significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.
doi:10.1017/S1355617707070488
PMCID: PMC2654607  PMID: 17445294
Magnetic Resonance Imaging; Self Assessment (Psychology); Agnosia; Alzheimer disease; Neocortex; Aging
23.  Roles of Education and IQ in Cognitive Reserve in Parkinson's Disease-Mild Cognitive Impairment 
Background/Aims
The role of cognitive reserve in Parkinson's disease (PD)-mild cognitive impairment (MCI) is incompletely understood.
Methods
The relationships between PD-MCI, years of education, and estimated premorbid IQ were examined in 119 consecutive non-demented PD patients using logistic regression models.
Results
Higher education and IQ were associated with reduced odds of PD-MCI in univariate analysis. In multivariable analysis, a higher IQ was associated with a significantly decreased odds of PD-MCI, but education was not.
Conclusion
The association of higher IQ and decreased odds of PD-MCI supports a role for cognitive reserve in PD, but further studies are needed to clarify the interaction of IQ and education and the impact of other contributors such as employment and hobbies.
doi:10.1159/000341782
PMCID: PMC3435526  PMID: 22962558
Parkinson's disease; Mild cognitive impairment; Education; IQ; Cognitive reserve
24.  Relation of Secondhand Smoking to Mild Cognitive Impairment in Older Inpatients 
The Scientific World Journal  2012;2012:726948.
Up to now, controversy still exists regarding the role of secondhand smoking (SHS) in developing cognitive impairment. This study aimed to evaluate the prevalence of SHS in hospitalized older patients with cognitive deficit, particularly in those with mild cognitive impairment (MCI). Smoking history was classified into four groups: never smokers, former-active smokers/no SHS, active smokers, and secondhand smokers, and cognitive function into three levels: normal cognition (C), MCI, and dementia. A total of 933 older subjects with diagnoses of MCI (n = 98), dementia (n = 124), or C (n = 711) were enrolled in this cross-sectional study. As expected, patients with dementia had significantly higher frequency of former-active smokers than cognitively normal. Moreover, patients with MCI showed a significantly higher frequency of active and secondhand smokers than patients with dementia or C. A smoking history is very frequent in older patients with dementia. Patients with MCI had even higher rate of exposure to active or secondhand smoking.
doi:10.1100/2012/726948
PMCID: PMC3361321  PMID: 22666146
25.  Neuropsychological characteristics of mild cognitive impairment subgroups 
Objective
To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study.
Methods
MCI was classified as MCI‐amnestic type (MCI‐AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI‐multiple cognitive deficits type (MCI‐MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition.
Results
MCI‐AT (n = 10) had worse verbal and non‐verbal memory performance than MCI‐MCDT (n = 28) or normal controls (n = 374). By contrast, MCI‐MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI‐AT or normal controls. MCI‐MCDT subjects had memory deficits, though they were less pronounced than in MCI‐AT. Of the MCI‐MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI‐MCDT with memory disorders had more language deficits than MCI‐MCDT without memory disorders. By contrast, MCI‐MCDT without memory deficits had more fine motor control deficits than MCI‐MCDT with memory deficits.
Conclusions
The most frequent form of MCI was the MCI‐MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI‐MCDT cases did not have memory impairment. Study of idiopathic amnestic and non‐amnestic forms of MCI is essential for an understanding of the aetiology of MCI.
doi:10.1136/jnnp.2004.045567
PMCID: PMC2077558  PMID: 16103044
Alzheimer's disease; aging; dementia; mild cognitive impairment; neuropsychology

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